Small aliphatic dicarboxylic acids inhibit renal uptake of administered mercury.
We evaluated the effects of pretreating rats intravenously with small aliphatic dicarboxylic acids on the renal disposition of injected inorganic mercury. Three different sets of experiments were carried out. When rats were pretreated with succinic acid, glutaric acid, or adipic acid 5 min prior to the injection of a 0.5-mumol/kg dose of mercuric chloride, there was a significant dose-dependent inhibitory effect on the renal disposition of mercury during the first hour after the administration of mercuric chloride. Both glutaric and adipic acid, at a dose of 1.0 mmol/kg, caused the greatest level of inhibition in the renal tubular uptake of inorganic mercury. By the end of the first hour after the injection of mercuric chloride, the renal burden of mercury in rats pretreated with either glutaric or adipic acid was 27-35% lower than in corresponding control rats. Malonic acid at a dose of 1.0 mmol/kg had no effect on the renal disposition of inorganic mercury. The inhibitory effect of succinic, glutaric, or adipic acid on the overall renal uptake of mercury was due to effects in both the cortex and outer stripe of the outer medulla. Findings from an experiment in which rats had their ureters ligated showed that the inhibitory effect of glutaric acid on the renal tubular uptake of mercury was due to inhibition of the uptake of mercury at the basolateral membrane. Our findings confirm that one of the mechanisms involved in the proximal tubular uptake of inorganic mercury is located on the basolateral membrane. According to findings from our previous studies, this mechanism appears to involve the activity of the organic anion transporter. The inhibitory effects of dicarboxylic acids on the renal tubular uptake of administered inorganic mercury, especially in rats whose ureters had been ligated, are consistent with the hypothesis that the organic anion transport system is involved in the basolateral uptake of inorganic mercury along the proximal tubule.
Zalups
R K
RK
Division of Basic Medical Sciences, Mercer University School of Medicine, Macon, Georgia 31207, USA.
Barfuss
D W
DW
D000272:Adipates / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D003998:Dicarboxylic Acids / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005977:Glutarates / Q000737:chemistry / Q000494:pharmacology; D007275:Injections, Intravenous; D007672:Kidney Cortex / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D007679:Kidney Medulla / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008314:Malonates / Q000737:chemistry / Q000494:pharmacology; D008627:Mercuric Chloride / Q000378:metabolism*; D008628:Mercury / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D019802:Succinic Acid / Q000737:chemistry / Q000494:pharmacology; D014018:Tissue Distribution
D000272:Adipates; D003998:Dicarboxylic Acids; D005977:Glutarates; D008314:Malonates; D008627:Mercuric Chloride; C029900:adipic acid; C030290:malonic acid; D019802:Succinic Acid; D008628:Mercury; C035736:glutaric acid